Interactions of Carbon Monoxide and Metabotropic Glutamate Receptor Groups in the Nucleus Tractus Solitarii of Rats

Lin, Chia‐Hui; Lo, Wan-Chen; Hsiao, Michael; Tung, Che‐Se; Tseng, Ching‐Jiunn

doi:10.1124/jpet.103.060186

Cited by 17 publications

(19 citation statements)

References 35 publications

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“…Fourth, the mGluR antagonist CPPG blocks responses to L-AP4 but is without effect on responses to NMDA or AMPA (54). Fifth, as discussed in detail later in the DISCUSSION, recent evidence indicates that L-AP4 but not NMDA produces its actions in NTS, at least in part, via the release of CO, which in turn may increase glutamate release (34,35). These data suggest that CO production may be an intermediary step by which L-AP4 enhances NMDA-mediated transmission without directly activating the NMDA receptor (34,35).…”

Section: Discussionmentioning

confidence: 99%

“…Fifth, as discussed in detail later in the DISCUSSION, recent evidence indicates that L-AP4 but not NMDA produces its actions in NTS, at least in part, via the release of CO, which in turn may increase glutamate release (34,35). These data suggest that CO production may be an intermediary step by which L-AP4 enhances NMDA-mediated transmission without directly activating the NMDA receptor (34,35). Finally, the results of the present study, discussed below, suggest that the cardiovascular effects of L-AP4 microinjection in the NTS are not mediated by L-AP4 or glycine contaminants acting at the glycine site on NMDA receptors.…”

Section: Discussionmentioning

confidence: 99%

“…For example, group III mGluRs generally are believed to be presynaptic and inhibit neurotransmitter release in different brain regions (6,16,42), including the NTS (4, 20, 25). However, recent reports indicate that microinjection of group III receptor agonists, such as L(ϩ)-2-amino-4-phosphonobutyric acid (L-AP4), into the NTS produces decreases in arterial pressure and sympathetic nerve activity, consistent with a net excitation of NTS neurons (34,36,54). …”

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confidence: 99%

“…Finally, we propose that responses to L-AP4 are due to an alteration in neurotransmitter release, possibly via group III mGluR-mediated production of carbon monoxide (CO; Refs. 34,35).…”

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confidence: 99%

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Cardiovascular response to a group III mGluR agonist in NTS requires NMDA receptors

Mueller

Foley

Vogl

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Previous studies have demonstrated that microinjection of the putative group III metabotropic glutamate receptor (mGluR) agonist, L(ϩ)-2-amino-4-phosphonobutyric acid (L-AP4), into the nucleus tractus solitarius (NTS) produces depressor and sympathoinhibitory responses. These responses are significantly attenuated by a group III mGluR antagonist and may involve ionotropic glutamatergic transmission. Alternatively, a previous report in vitro suggests that preparations of L-AP4 may nonspecifically activate NMDA channels due to glycine contamination (Contractor A, Gereau RW, Green T, and Heinemann SF. Proc Natl Acad Sci USA 95: 8969 -8974, 1998).Therefore, the present study tested whether responses to L-AP4 specifically require the N-methyl-D-aspartate (NMDA) receptor and whether they are due to actions at the glycine site on the NMDA channel. To test these possibilities in vivo, we performed unilateral microinjections of L-AP4, glycine, and selective antagonists into the NTS of urethane-anesthetized rats. L-AP4 (10 mM, 30 nl) produced sympathoinhibitory responses that were abolished by the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (AP-5, 10 mM) but were unaffected by the non-NMDA antagonist 6-nitro-7-sulfamobenzoquinoxaline-2,3-dione (NBQX, 2 mM). Microinjection of glycine (0.02-20 mM) failed to mimic sympathoinhibitory responses to L-AP4, even in the presence of the inhibitory glycine antagonist, strychnine (3 mM). Strychnine blocked pressor and sympathoexcitatory actions of glycine (20 mM) but failed to reveal a sympathoinhibitory component due to presumed activation of NMDA receptors. The results of these experiments suggest that responses to L-AP4 require NMDA receptors and are independent of non-NMDA receptors. Furthermore, although it is possible that glycine contamination or other nonspecific actions are responsible for the sympathoinhibitory actions of L-AP4, our data and data in the literature argue against this possibility. Thus we conclude that responses to L-AP4 in the NTS are mediated by an interaction between group III mGluRs and NMDA receptors. Finally, we also caution that nonselective actions of L-AP4 should be considered in future studies.L-2-amino-4-phosphonobutyric acid; microinjection; metabotropic glutamate receptors; sympathetic nerve activity; nucleus tractus solitarius; N-methyl-O-aspartate THE NUCLEUS TRACTUS SOLITARIUS (NTS) is the primary termination site for baroreceptor afferents and is an important site for control of sympathetic outflow (47). Because glutamate appears to be the primary neurotransmitter of baroreceptor afferents (47, 50) and metabotropic glutamate receptors (mGluRs) are present in the NTS (4, 24, 25, 39), we and others have postulated that mGluRs may subserve various functions within the NTS (4,15,18,19,38). For example, group III mGluRs generally are believed to be presynaptic and inhibit neurotransmitter release in different brain regions (6,16,42), including the NTS (4, 20, 25). However, recent reports indicate that microinjection of group III recep...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…Finally, we propose that responses to L-AP4 are due to an alteration in neurotransmitter release, possibly via group III mGluR-mediated production of carbon monoxide (CO; Refs. 34,35).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Cardiovascular response to a group III mGluR agonist in NTS requires NMDA receptors

Mueller

Foley

Vogl

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The neural effects of heme oxygenase are generally different from those of nitric oxide (NO) synthase (23). Recent studies have demonstrated that CO is involved in central cardiovascular regulation and modulates the baroreflex in the nucleus tractus solitarii of rats (24,25). The present study investigated the possible role of ACPC in the regulation of HO-1 expression and antioxidant effects in stroke-prone spontaneously hypertensive rats (SHRSP).…”

Section: Introductionmentioning

confidence: 94%